ESTRO 35 Abstract-book

ESTRO 35 2016 S969 ________________________________________________________________________________

Conclusion: The relocalization of peripheral leukocytes in the damaged tissue depends on the radiation dosage and it may be evaluated by means of a non-invasive imaging technique. Further analyses are currently ongoing. EP-2054 Expression of DNA-PK in squamous cell lung cancer has gender differences and depends on smoking J. Jaal 1 , L. Mägi 1 , T. Jõgi 2 , M. Kase 3 , A. Minajeva 1 , V. Markus 2 , T. Vooder 4 , R. Roosipuu 5 , J. Jaal 1 University of Tartu, Faculty of Medicine, Tartu, Estonia 2 2 Tartu University Hospital, Dept of Radiotherapy and Oncological Therapy, Tartu, Estonia 3 East-Tallinn Central Hospital, Cancer Centre, Tallinn, Estonia 4 Centre for Thoracic Diseases, Dept of Thoracic Surgery, Ruhr, Germany 5 Tartu University Hospital, Dept of Pathology, Tartu, Estonia Purpose or Objective: Lung cancer is one of the most frequent and deadly types of cancer in Europe. Several aspects of non-small cell lung cancer (nsclc) in men and women continue to indicate potential male-female differences. Among these, higher treatment responses to current therapies in women are supposed, since women have better prognosis in any stage of the disease. In most stages of nsclc cytotoxic anti-cancer therapy (radiotherapy, chemotherapy) is used. It is known that treatment efficacy of cytotoxic anti-cancer therapy depends on tumor DNA-repair. Therefore, the aim of this study was to evaluate gender differences in the expression of DNA repair enzyme DNA protein kinase (DNA-PK). Material and Methods: Surgically excised nsclc tissues (n=111, 50 adenocarcinomas, 61 squamous cell carcinomas) were examined for DNA-PK expression. After immunohistochemistry, the staining intensity of DNA-PK was quantified using an arbitrary score ranging from 0 (no staining) to 3 (strong signal). Also, the proportion (%) of DNA- PK positive (DNA-PK+) tumor cells was determined. All parameters were examined by 2 independent researchers in 10 randomly chosen microscopic fields (magnification x40). Results: Immunohistochemical parameters were examined by 2 independent researchers whose results were in good accordance (p<0.0005). Staining intensities of DNA-PK and the proportion of DNA-PK+ tumor cells varied, being in the whole nsclc group 2.4±0.4 (mean±SD) and 86.3±9.1% respectively. There were no significant gender differences in adenocarcinoma. However, we detected significant differences among nsclc patients with squamous cell carcinoma. Both, DNA-PK staining intensity and the proportion of DNA-PK+ tumor cells were significantly higher in men than in women, 2.5±0.3 and 86.3±8.8% vs 2.1±0.6 and 79.6±11.9% respectively (DNA-PK intensity: p<0.01; DNA-PK+ proportion: p=0,03). Additionally, we found that in squamous cell carcinoma, the expression of DNA-PK depends on smoking and pack-years. There was a correlation between pack-years and DNA-PK intensity (p=0.04), as well as between pack-years and the proportion of DNA-PK+ tumor cells (p=0.04). Conclusion: Expression of DNA-PK in squamous cell lung cancer has gender differences and depends on smoking. Significantly lower expression of tumor DNA-PK was found in women with this histological subtype of nsclc. Latter might be one of the reasons why cytotoxic anti-cancer therapy is more efficacious in women than in men. In further studies, the combination of DNA repair inhibitors and cytotoxic anti- cancer therapy should be tested. EP-2055 Fibro-inflammatory circulating proteins as biomarkers for response in locally advanced rectal cancer P. Bulens 1,2 , A. Debucquoy 2 , I. Joye 1,2 , O. De Wever 3 , A. Wolthuis 4 , A. D'Hoore 4 , E. Van Cutsem 5 , V. Vandecaveye 6 , X. Sagaert 7 , C. Deroose 8 , O. Gevaert 2,9 , K. Haustermans 1,2 1 University Hospital Leuven, Radiation Oncology, Leuven, Belgium 2 University of Leuven, Oncology, Leuven, Belgium

Material and Methods: A rat model was used to investigate a possible selective accumulation of circulating lymphocites to specific anatomical districts after radiation treatment focused to the urinary bladder. Eight Fisher rats were adoptively transferred with 4x107 VivoTag-750-labelled syngeneic primary splenocytes at two hours before the bladder irradiation. Two of eight rats were used as controls. Animals were transurethrally catheterized to allow contrast agent instillation. A kV cone beam computed tomography (CBCT) was acquired for each rat, to precisely deliver 6 MeV monofraction photon field. Rats were divided into three groups (n=2/group) receiving different levels of dose: 15, 20 and 25 Gy. A bolus thickness equal to 1cm was positioned on the rat skin surface in the pelvic region. Ultrasound images of the pelvic region were acquired at baseline, at 2, 4 and 6 days after irradiation to monitor thickness variations of the bladder wall tissue. In vivo fluorescent imaging was used to evaluated accumulation sites of labelled leukocytes. Results: A significant increase in the bladder wall thickness was found 4 days after irradiation in animals treated with a dose equal to 25 Gy. A fluorescent signal, secondary to labelled splenocytes accumulation, emerged in the liver and lymph nodes of all adoptively transferred rats, 2 and 6 days after irradiation, as expected. A modest specific signal (30% increase) at the bladder level resulted only in two animals receiving the higher dose (Figure 1.a), when compared to the non-irradiated (Figure 1.b). No specific fluorescent signal was detected at the bladder levels in animals treated with 20 and 15 Gy.